Caltech Scientist Creates New Method for Folding Strands of DNA to Make Microscopic Structures

PASADENA, Calif.—In a new development in nanotechnology, a researcher at the California Institute of Technology has devised a way of weaving DNA strands into any desired two-dimensional shape or figure, which he calls "DNA origami."

According to Paul Rothemund, a senior research fellow in computer science and computation and neural systems, the new technique could be an important tool in the creation of new nanodevices, that is, devices whose measurements are a few billionths of a meter in size.

"The construction of custom DNA origami is so simple that the method should make it much easier for scientists from diverse fields to create and study the complex nanostructures they might want," Rothemund explains.

"A physicist, for example, might attach nano-sized semiconductor 'quantum dots' in a pattern that creates a quantum computer. A biologist might use DNA origami to take proteins which normally occur separately in nature, and organize them into a multi-enzyme factory that hands a chemical product from one enzyme machine to the next in the manner of an assembly line."

Reporting in the March 16th issue of Nature, Rothemund describes how long single strands of DNA can be folded back and forth, tracing a mazelike path, to form a scaffold that fills up the outline of any desired shape. To hold the scaffold in place, 200 or more DNA strands are designed to bind the scaffold and staple it together.

Each of the short DNA strands can act something like a pixel in a computer image, resulting in a shape that can bear a complex pattern, such as words or images. The resulting shapes and patterns are each about 100 nanometers in diameter-or about a thousand times smaller than the diameter of a human hair. The dots themselves are six nanometers in diameter. While the folding of DNA into shapes that have nothing to do with the molecule's genetic information is not a new idea, Rothemund's efforts provide a general way to quickly and easily create any shape. In the last year, Rothemund has created half a dozen shapes, including a square, a triangle, a five-pointed star, and a smiley face-each one several times more complex than any previously constructed DNA objects. "At this point, high-school students could use the design program to create whatever shape they desired,'' he says.

Once a shape has been created, adding a pattern to it is particularly easy, taking just a couple of hours for any desired pattern. As a demonstration, Rothemund has spelled out the letters "DNA," and has drawn a rough picture of a double helix, as well as a map of the western hemisphere in which one nanometer represents 200 kilometers.

Although Rothemund has hitherto worked on two-dimensional shapes and structures, he says that 3-D assemblies should be no problem. In fact, researchers at other institutions are already using his method to attempt the building of 3-D cages. One biomedical application that Rothemund says could come of this particular effort is the construction of cages that would sequester enzymes until they were ready for use in turning other proteins on or off.

The original idea for using DNA to create shapes and structures came from Nadrian Seeman of New York University. Another pioneer in the field is Caltech's Assistant Professor of Computer Science and Computation and Neural Systems Erik Winfree, in whose group Rothemund works.

"In this research, Paul has scored a few unusual `firsts' for humanity," Winfree says. "In a typical reaction, he can make about 50 billion 'smiley-faces.' I think this is the most concentrated happiness ever created.

"But the applications of this technology are likely to be less whimsical," Winfree adds. "For example, it can be used as a 'nanobreadboard' for attaching almost arbitrary nanometer-scale components. There are few other ways to obtain such precise control over the arrangement of components at this scale."

The title of the Nature paper is "Folding DNA to create nanoscale shapes and patterns."